Kidney Res Clin Pract.  2017 Mar;36(1):68-78. 10.23876/j.krcp.2017.36.1.68.

Sustained uremic toxin control improves renal and cardiovascular outcomes in patients with advanced renal dysfunction: post-hoc analysis of the Kremezin Study against renal disease progression in Korea

Affiliations
  • 1Department of Internal Medicine, National Medical Center, Seoul, Korea.
  • 2Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
  • 3Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
  • 4Department of Internal Medicine, Korea University Ansan-Hospital, Korea University College of Medicine, Seoul, Korea.
  • 5Department of Internal Medicine, Seoul National University Bundang Hopsital, Seongnam, Korea.
  • 6Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. yonsukim@snu.ac.kr
  • 7Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea.
  • 8Department of Internal Medicine, Uijeongbu St. Mary's Hospital, The Catholic University of Korea, Uijeongbu, Korea.
  • 9Department of Internal Medicine, Inje University Ilsan-Paik Hospital, Goyang, Korea.
  • 10Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea.
  • 11Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University of Medicine and Science, Incheon, Korea.
  • 12Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea.
  • 13Kidney Research Institute, Seoul National University, Seoul, Korea.

Abstract

BACKGROUND
We investigated the long-term effect of AST-120, which has been proposed as a therapeutic option against renal disease progression, in patients with advanced chronic kidney disease (CKD).
METHODS
We performed post-hoc analysis with a per-protocol group of the K-STAR study (Kremezin study against renal disease progression in Korea) that randomized participants into an AST-120 and a control arm. Patients in the AST-120 arm were given 6 g of AST-120 in three divided doses, and those in both arms received standard conventional treatment.
RESULTS
The two arms did not differ significantly in the occurrence of composite primary outcomes (log-rank P = 0.41). For AST-120 patients with higher compliance, there were fewer composite primary outcomes: intermediate tertile hazard ratio (HR) 0.62, 95% confidence interval (CI) 0.38 to 1.01, P = 0.05; highest tertile HR 0.436, 95% CI 0.25 to 0.76, P = 0.003. The estimated glomerular filtration rate level was more stable in the AST-120 arm, especially in diabetic patients. At one year, the AST-120-induced decrease in the serum indoxyl sulfate concentration inversely correlated with the occurrence of composite primary outcomes: second tertile HR 1.59, 95% CI 0.82 to 3.07, P = 0.17; third tertile HR 2.11, 95% CI 1.07 to 4.17, P = 0.031. Furthermore, AST-120 showed a protective effect against the major cardiovascular adverse events (HR 0.51, 95% CI 0.26 to 0.99, P = 0.046).
CONCLUSION
Long-term use of AST-120 has potential for renal protection, especially in diabetic patients, as well as cardiovascular benefits. Reduction of the serum indoxyl sulfate level may be used to identify patients who would benefit from AST-120 administration.

Keyword

Advanced renal dysfunction; AST-120; Cardiovascular outcome; Renal outcome; Uremic toxin

MeSH Terms

Arm
Compliance
Disease Progression*
Glomerular Filtration Rate
Humans
Indican
Korea*
Renal Insufficiency, Chronic
Indican
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